There are a number of other current and potential uses for detection and identification of volatile compounds. For example, different chemical analyses have been used to detect the presence or absence of a known target chemical in clinical diagnoses, to identify unknown compounds and mixtures in basic research and drug discovery, and to document the identity and purity of known compounds, e.g., in testing and quality control in drug manufacturing processes. In addition to laboratory analyses, chemical detection is also important outside of the laboratory. Examples include bedside diagnoses, and environmental monitoring for hazardous materials. The “field” applications, including detection of explosives and chemical warfare agents, require small, portable, reliable, easy-to-use, inexpensive devices.
The serious threat of explosive, chemical and/or biological attacks pose a particular challenge for national security in the current “post September 11th” era. A method that could detect a wide range of compounds, and that could also be automated and remotely controlled and that could be used in field conditions including airport, seaport, or other screening systems, would be particularly desirable. For example, currently only about 2% of all the containers are screened by any means that come through the seaports to the United States, because there are no suitable reliable, fast, easy and relatively cheap screening methods available. For national security, it is imperative to develop screening methods that could detect, for example, explosives and toxic chemicals that may be transported into the United States. Detection methods for identifying trace amounts of volatile compounds from, for example, explosives or chemical warfare agents, would be one possible way to approach such novel screening methods for national security purposes.
There are a number of methods currently available for chemical analysis, each appropriate for a particular application and each having its own strengths and weaknesses. Examples include the various forms of chromatography, including gas chromatography (GC), high performance liquid chromatography (HPLC), and spectroscopy, including mass spectroscopy (MS), ion mobility spectroscopy (IMS), Raman spectroscopy and infrared spectroscopy, as well as other chemical, immunological, and gravimetric methods. Also, combinations of different methods can provide a powerful means of identifying unknown compounds, e.g., GC/MS which is used extensively in analytical chemistry laboratories.
A common feature of these analytical methods is that the chemical sample needs to be prepared prior to analysis. Liquid and solid samples are usually dissolved into an appropriate solvent. For analysis of vapor-phase chemicals, a preconcentration step is often required to increase the quantity of material for analysis.
Preconcentration of vapor-phase chemicals involves, for example, passing a large volume of air over an adsorbent Tenax or solid phase microextraction (SPME) trap. The sample is removed from the trap using a small amount of liquid solvent or is thermally desorbed directly into the input of a GC for analysis (Zhang, Z., Yang, M. J., and Pawliszyn, J. (1994). Anal. Chem., 66:844A–853A).
Preconcentration followed by GC or GC/MS has been used to detect and quantify volatile chemicals in a variety of studies with relevance to health care and domestic security, for example, detection of contaminants in water (Lambropoulou, D. A. and Albanis, T. A. (2001). J. Chromatogr., 922:243–255; Cancho, B., Ventura, F., and Galceran, M. T. (2002). J. Chromatogr., 943:1–13) and soils (Cam, D. and Gagni, S. (2001). J. Chromatogr. Sci., 39:481–486), detection of toxic substances in blood (Bouche, M. P., Lambert, W. E., Bocxlaer, J. F. V., Piette, M. H., and Leenheer, A. P. D. (2001). J. Anal. Toxicol., 26:35–42; Musshoff, F., Junker, H., and Madea, B. (2002). J. Chromatogr. Sci., 40:29–34), detection of drugs in postmortem tissue (Mosaddegh, M. H., Richardson, R., Stoddart, R. W., and McClure, J. (2001). Ann. Clin. Biochem., 38:541–547), detection of organic compounds in normal breath (Grote, C. and Pawliszyn, J. (1997). Anal. Chem., 69:587–596) and in the breath of lung cancer patients (Phillips, M., Gleeson, K., Hughes, J. M. B., Greenberg, J., Cataneo, R. N., Baker, L., and McVay, W. P. (1999). Lancet, 353:1930–1933), characterization of explosive signatures (Jenkins, T. F., Leggett, D. C., Miyares, P. H., Walsh, M. E., Ranney, T. A., Cragin, J. H., and George, V. (2001). Talanta, 54:501–513), and detecting Sarin in air and water (Schneider, J. F., Boparai, A. S., and Reed, L. L. (2001). J. Chromatogr. Sci., 39:420–424). For rapid detection of volatile compounds, it would be advantageous to avoid specific sample preparation steps. This would be especially desirable in applications where detection is performed in field conditions, outside a laboratory.
Volatile chemical analyses using these methods require optimizations for each analysis problem. For example, the GC column, GC detector, trap coatings, and flow rates all need to be optimized for particular volatiles of interest. In addition, preconcentration can take considerable time to collect sufficient material in the trap. The time required depends on the sorbent coating on the trap (different Tenax coatings have different affinities for different chemical compounds) and on the original concentration of sample in the air. Such analytical methods are therefore generally inappropriate for rapid analyses, such as security screening, real-time environmental monitoring, or bedside diagnoses. Therefore, it would be advantageous to develop a detection system that is capable of rapidly analyzing a wide array of different compounds in varying concentrations.
For air sampling, an alternative to preconcentration consists of systems containing dedicated sensors that are responsive to particular compounds of interest. Common examples include home detectors for carbon monoxide, propane, and natural gas. Although sensors are available that are broadly responsive, e.g., sensors that respond to many volatile organic compounds, these devices do not identify the vapor detected. While a system containing a dedicated sensor can respond rapidly and may not require preconcentration, the ability to detect and identify multiple volatile compounds would require a separate sensor selective for each compound of interest. Further, such methods preclude detection of future compounds of interest. Therefore, it would be desirable to develop a system that is capable of sensing as well as identifying a wide range of compounds.
For detecting, discriminating, and identifying volatile compounds in the air, one of the most highly developed chemical detection devices is arguably the olfactory system of terrestrial animals. Olfactory abilities include high sensitivity (Passe, D. H. and Walker, J. C. (1985). Neurosci. Biobehav. Rev., 9:431–467), the ability to detect and discriminate many different compounds (e.g., Youngentob, S. L., Markert, L. M., Mozell, M. M., and Hornung, D. E. (1990). Physiol. Behav., 47:1053–1059; Slotnick, B. M., Kufera, A., and Silberberg, A. M. (1991). Physiol. Behav., 50:555–561; Lu, X.-C. M., Slotnick, B. M., and Silberberg, A. M. (1993). Physiol. Behav., 53:795–804), and the ability to make fine odorant discriminations (e.g., individual recognition in rodents—Yamazaki, K., Singer, A., and Beauchamp, G. K. (1998–1999). Genetica, 104:235–240). Numerous mechanisms influence these capabilities at points in the process even before odorant molecules interact with receptor proteins. Sniffing behavior, nasal aerodynamics, mucus solvation, and odorant clearing all likely play a role in olfactory abilities (Christensen, T. A. and White, J. (2000). Representation of olfactory information in the brain. In Finger, T. E., Silver, W. L., and Restrepo, D., editors, Neurobiology of Taste and Smell, pages 201–232. John Wiley & Sons, New York). Once odorants reach the olfactory receptor proteins in the nasal mucosa, the system does not devote one receptor protein to each individual odorous ligand. Rather, even single compounds interact with many broadly-responsive receptor proteins, producing widespread spatiotemporal patterns of activity in the olfactory sensory neuron population—in other words, activity in many sensor elements that evolve over time (MacKay-Sim, A., Shaman, P., and Moulton, D. G. (1982). J. Neurophysiol., 48:584–596; Kent, P. F. and Mozell, M. M. (1992). J. Neurophysiol, 68:1804–1819). These patterns of activity are then interpreted by parallel processing elements in the olfactory areas of the brain, producing widespread activation in the neuronal populations at each level of the olfactory pathway (for reviews, see Kauer, 1987 Kauer, J. S. (1987). Coding in the olfactory system. In Finger, T. E. and Silver, W. L., editors, Neurobiology of Taste and Smell, pages 205–231. John Wiley & Sons, Inc, New York; Kauer, J. S. (1991). Trends Neurosci, 14:79–85; Christensen, T. A. and White, J. (2000). Representation of olfactory information in the brain. In Finger, T. E., Silver, W. L., and Restrepo, D., editors, Neurobiology of Taste and Smell, pages 201–232. John Wiley & Sons, New York).
The properties of the olfactory system suggest that engineered devices based on olfactory mechanisms may have advantages for detecting and identifying volatile compounds. Such a device, called an “artificial nose” or “electronic nose,” was first described in the early 1980's (Persaud, K. and Dodd, G. (1982). Nature, 299:352–355), and a number of systems have been reported since then (see, e.g., Grate, J. W., Rose-Pehrsson, S. L., Venezky, D. L., Klusty, M., and Wohltjen, H. (1993). Anal. Chem., 65:1868–1881; Freund, M. S. and Lewis, N. S. (1995). Proc. Nat. Acad. Sci. USA, 92:2652–2656; White, J., Kauer, J. S., Dickinson, T. A., and Walt, D. R. (1996). Anal. Chem., 68:2191–2202). All of these devices incorporate the two main features that define an electronic nose: 1) an array of broadly-responsive sensors and 2) a pattern recognition method for processing sensor output. Like in the olfactory system, odorants interact with multiple sensors, producing a pattern of activation across the array. Commercial and research electronic noses use a variety of technologies for chemical sensing including conducting polymers, surface acoustic wave devices, solid-state devices, and optical interrogation. Pattern recognition methods generally involve statistical methods or computational neural networks (for reviews, see Gardner, J. W. and Bartlett, P. N., editors (1992). Sensors and sensory systems for an electronic nose. Kluwer Academic Publishers, Dordrecht, The Netherlands; Gardner, J. W. and Bartlett, P. N. (1994). Sensors and Actuators B, 18–19:211–220; Gardner, J. W. and Hines, E. L. (1997). Pattern analysis techniques. In Kress-Rogers, E., editor, Handbook of Biosensors and Electronic Noses: Medicine, Food, and the Environment, pages 633–652. CRC Press, Boca Raton, Fla.; Dickinson, T. A., White, J., Kauer, J. S., and Walt, D. R. (1998). Trends Biotechnol., 16:250–258). Potential and actual uses of commercial electronic noses include food/beverage analysis, environmental monitoring, and medical diagnosis (Ping, W., Yi, T., Haibao, X., and Farong, S. (1997). Biosens. Bioelectron., 12:1031–1036; Dickinson, T. A., White, J., Kauer, J. S., and Walt, D. R. (1998). Trends Biotechnol., 16:250–258; Aathithan, S., Plant, J. C., Chaudry, A. N., and French, G. L. (2001). J. Clin. Microbiol., 39:2590–2593).
Vapor phase chemical detection systems based on arrays of broadly-responsive sensors offer a number of potential advantages over traditional analytical devices. An electronic nose directly samples the air, so no sample preparation is necessary. The time required for detection is limited only by the time required for the chemical sensors to respond and for the pattern recognition calculation, which is fast using modern computer technology. With rapidly-responding sensors, rapid detection of volatiles is therefore possible. In addition, while traditional analytical instruments tend to be large and require considerable power, sensor array devices have the potential for being small and portable. Although handheld IMS devices are available, they are currently tuned to specific, restricted tasks, such as use of the Iontrack Instruments VaporTracer2 for explosives or drugs, and therefore lack the broad-band nature of an electronic nose.
Sensor array devices also would also have a number of advantages over systems using mono-specific sensors. First, truly “mono-specific” sensors are difficult (if not impossible) to produce; broadly-responsive sensors can be readily made. Second, even if mono-specificity could be achieved, detection of several compounds would require development of a separate sensor for each compound of interest. Conversely, a relatively small array of broadly-responsive sensors is theoretically capable of discriminating a large number of different compounds (Alkasab, T. K., White, J., and Kauer, J. S. (2002). Chem. Senses, 27:261–275). Third, a device containing sensors specific for a finite number of compounds is incapable of detecting any others outside its defined target set. A device containing broadly-responsive sensors would have the potential for detecting and discriminating compounds of future interest.
It would be advantageous to develop sensors capable of detecting and correctly identifying a large range of volatile chemicals. Such sensors would be particularly useful in domestic security applications, such as detecting explosives and chemical warfare agents.